Uninjured tissues and organs of the body are composed of different cell types, and extracellular matrices that affect cell, tissue and organ functions. Noncongenital injury to cells and tissues causes wounds and initiates common mechanisms of wound healing at all sites in the body (Robbins S. L. et al, (Eds.) "Pathologic Basis of Disease", 2nd ed Philadelphia: W. B. Saunders, 1979:55-106). Fundamental components of wound closure include restoration of stable ectoderm-derived tissue (epithelium or endothelium) and of uniform vascular supply in the adjacent mesoderm-derived tissue. For optimal closure, wounds caused by traumatic injury or elective surgery require rapid restoration of normal tissue anatomy in the absence of infection (Bucknell T. E., et al. (Eds.) "Wound healing for surgeons", Philadelphia: Bailliere Tindall, 1984: 42-74).
In the last decade, technological achievements in the in vitro culture of human epithelial cells has attracted a remarkable interest for its therapeutic application. The most striking practical application is undoubtedly the successful use of in vitro cultured epithelial sheets as autografts on patients with extensive tegumental losses (Green H. et al., 1979, Proc. Natl. Acad. Sci. USA, 76: 5665; Gallico G. et al., 1984, N. Eng. J. Med., 31:448). It has been shown that a biopsy specimen of 1 to 2 cm.sup.2 can be expanded in surface area by a factor of 10,000 when cultured in vitro.
Early excision of full skin thickness burns followed by grafting of autologous meshed skin have decreased the mortality rate of patients suffering from large burn wounds (Heimbach D. M., M.D. 1987, Surg. Clin. North. Am., 67: 93). However, burns covering more than 50% of the total body surface lead to very high mortality rates which are directly related to the limited availability of donor sites for epithelium split thickness meshed grafts. In vitro reconstructed human epithelium has been successfully used since 1981 in the treatment of major burns (O'Connor et al, 1981, Lancet, Jan. 10, 1975). This process presents a high level of success for burned patients wounded over 50% of their body surface. However, the long time interval (3 to 5 weeks) required for cell growth and graftable sheets production, a period during which the patient may become progressively ill, is a major disadvantage of this technique. One of our interests is to provide quick and safe methods for skin trauma therapy. This critical goal may be reached by the below described invention.